Adhatoda Vasica attenuates inflammatory and hypoxic responses in preclinical mouse models: potential for repurposing in COVID-19-like conditions

Background COVID-19 pneumonia has been associated with severe acute hypoxia, sepsis-like states, thrombosis and chronic sequelae including persisting hypoxia and fibrosis. The molecular hypoxia response pathway has been associated with such pathologies and our recent observations on anti-hypoxic and anti-inflammatory effects of whole aqueous extract of Adhatoda Vasica (AV) prompted us to explore its effects on relevant preclinical mouse models. Methods In this study, we tested the effect of whole aqueous extract of AV, in murine models of bleomycin induced pulmonary fibrosis, Cecum Ligation and Puncture (CLP) induced sepsis, and siRNA induced hypoxia-thrombosis phenotype. The effect on lung of AV treated naive mice was also studied at transcriptome level. We also determined if the extract may have any effect on SARS-CoV2 replication. Results Oral administration AV extract attenuates increased airway inflammation, levels of transforming growth factor-beta 1 (TGF-beta 1), IL-6, HIF-1 alpha and improves the overall survival rates of mice in the models of pulmonary fibrosis and sepsis and rescues the siRNA induced inflammation and associated blood coagulation phenotypes in mice. We observed downregulation of hypoxia, inflammation, TGF-beta 1, and angiogenesis genes and upregulation of adaptive immunity-related genes in the lung transcriptome. AV treatment also reduced the viral load in Vero cells infected with SARS-CoV2. Conclusion Our results provide a scientific rationale for this ayurvedic herbal medicine in ameliorating the hypoxia-hyperinflammation features and highlights the repurposing potential of AV in COVID-19-like conditions.

Automated summary

The whole aqueous extract of Adhatoda Vasica showed promising effects in attenuating airway inflammation, reducing levels of TGF-beta 1, IL-6, and HIF-1 alpha, improving survival rates in pulmonary fibrosis and sepsis murine models, and rescuing inflammation and blood coagulation phenotypes induced by siRNA. It also downregulated hypoxia-related genes and upregulated genes related to adaptive immunity in lung transcriptome, while reducing viral load in SARS-CoV2 infected cells, suggesting potential for repurposing in COVID-19-like conditions.